A three-in-one nanoplatform with photo/chemodynamic activities combined with glutathione depletion for treating bacterial infections

Abstract

The misuse of antibiotics leading to bacterial multidrug resistance is responsible for severe infectious diseases and a significant cause of mortality worldwide, resulting in numerous human disasters. Photodynamic antibacterial therapy (PDAT) is a promising strategy against multiantibiotic-resistant bacteria, but its antibacterial activity is greatly limited by reduced glutathione (GSH) in bacteria. In this study, we constructed a nanoplatform through the formation of metal chelating complexes (FeP) between ferric and pyrophosphate ions, with subsequent adsorption of the photosensitizer ZnPc(COOH)8 (octa-carboxyl substituted zinc phthalocyanine) mediated by polylysine (PL) on the surface. The nanocomplexes FeP@PL:ZnPc(COOH)8 exhibited the capacity of GSH depletion and chemodynamic activity, which synergistically enhanced PDAT efficacy. FeP@PL:ZnPc(COOH)8 possessed the excellent antibacterial activity in vivo and in vitro, which might be attributed to the increased production of reactive oxygen species (ROS), reduced GSH level in bacteria, improved bacterial uptake, and enhanced destruction of the bacterial outer membrane. Moreover, FeP@PL:ZnPc(COOH)8 exhibited accelerated wound healing efficacy and the ability to recognize bacteria-infected wounds, rendering it an effective theranostic nanoplatform for bacterial infections. The construction strategy of nanocomplexes in this study holds theoretical and practical significance for high-efficiency synergistic photodynamic and chemodynamic antibacterial therapy.